Kit for measuring analytes

ABSTRACT

Devices, systems, methods and kits are provided for use in determining the concentration of chemical and biochemical components in aqueous fluids. The subject devices include test strips which define a longitudinal axis and include a distal edge configured for insertion into a measurement instrument and having an alignment notch formed in the distal edge for engagement with an alignment member of the measurement instrument. The alignment notch has opposing edges wherein at least a portion of the opposing edges is in substantially parallel relation to the longitudinal axis. In using the subject devices, the devices are inserted into a measurement instrument having an alignment pin. When operatively engaged with the alignment pin, the notch serves to maintain the device in a substantially motionless position. The invention is useful in a variety of applications, particularly in the determination of blood glucose concentrations.

This Application is a Divisional of Ser. No. 09/884,368 filed Jun. 19,2001, which is incorporated herein by reference in its entirety now U.S.Pat. No. 6,576,416.

FIELD OF THE INVENTION

The present invention is related to the field of medical diagnosticdevices for determining the concentration of chemical and biochemicalcomponents (analytes) in aqueous fluids. Particularly, the presentinvention is directed to measuring the concentration of an analyte in,or a property of, a biological fluid such as blood and more particularlyglucose in blood.

BACKGROUND OF THE INVENTION

The quantification or assay of chemical and/or biochemical constituentswithin biological fluids, such as blood, urine, and saliva, and withinbiological fluid fractions or derivatives such as blood serum and bloodplasma, is of ever increasing importance for medical diagnosis andtreatment, as well as the quantification of exposure to therapeuticdrugs, intoxicants, hazardous chemicals, and the like. One such commonapplication is the measurement of blood glucose levels in diabetics.

Widely accepted assays involve measuring a change in a physicalcharacteristic of the fluid being tested or an element of such fluidwhen exposed to a particular energy source. These physicalcharacteristics are typically an electrical, magnetic, fluidic, oroptical property of the fluid or a component thereof. For example, witha colorimetric assay system, an optical property may be monitoredwherein a change in light absorption of the fluid can be related to ananalyte concentration in, or a property of, the fluid.

To carry out the assays, a disposable test strip, pad, or the like, isemployed in conjunction with a meter. A sample of the biological fluidto be tested is provided. When the biological fluid is blood, a sampleis typically acquired by means of a finger stick. The fluid sample isthen deposited in a designated measurement area of the test strip, whichcontains reagents selected for the particular assay being conducted. Thetest strip, or at least a portion thereof, is placed in a receptaclearea or test strip holder within the meter. The meter is capable ofreceiving a signal originating in a measurement area of the test stripand determining the existence and/or concentration of the constituent oranalyte of interest. Examples of assay systems that employ these typesof disposable test strips and meters may be found in U.S. applicationSer. No. 09/333,765, filed Jun. 15, 1999, and Ser. No. 09/356,248, filedJul. 16, 1999; and in U.S. Pat. Nos. 4,935,346, 5,049,487, 5,304,468 and5,563,042, the disclosures of which are herein incorporated byreference.

Often, the measurement area of the test strip is defined by a smallaperture within the surface of the test strip. Placed over and coveringthe aperture on one side of the test strip is a hydrophilic material,e.g., a membrane, matrix, layer, or the like, containing reagent(s)suitable for determining the existence and/or the concentration of theparticular analyte of interest. The sampled fluid is deposited on theopposite side of the test strip within the aperture whereby the fluid isthen absorbed into the hydrophilic matrix. Such a test stripconfiguration is used, for example, in colorimetric measurement systems;see, e.g., U.S. Pat. No. 5,563,042. Such systems employ meters, such asa diffuse reflectance spectrophotometer with accompanying software,which can be made to automatically transmit a light source at aparticular wavelength and then read reflectance, of the test sample atcertain points in time, and, using calibration factors, determine theconcentration of analyte in the sampled fluid.

In order to obtain an accurate measurement of the fluid sample depositedwithin the aperture, it is necessary to properly position the test stripwithin the test strip holder and align the aperture of the test stripwith the light source, typically a high-intensity light emitting diode(LED), within the meter. Improper positioning of the test strip canresult, for example, from a slight rebound of the test strip as itsdistal or insertion end is caused to contact the edge of the stripholder. Also, some shifting or slipping or the test strip may occurafter it has been placed within the meter.

To facilitate proper positioning and alignment of the test strip withinthe test strip holder, a notch or a cut-out is formed within an edge ofa test strip which is to be aligned with a corresponding or matingalignment pin within the inner edge of the test strip holder. This hasnot been completely successful as the strip is still able, to somedegree, to shift from side-to-side when the strip is not fully inserted.Such movement or “play” in the position of the test strip increases thelikelihood that the test strip will be improperly or not completelyinserted or misaligned within the meter. As a result of thismisalignment, the measurement aperture of the test strip may not becentered with respect to the light source, which may then result in anincorrect measurement.

Often, to compensate for this likelihood of misalignment and theresulting incorrect measurement, a larger aperture requiring a greatervolume of the biological fluid, e.g., blood, being tested is used so asto provide a larger measurement area within the test strip. Adisadvantage of using a greater volume of sampled fluid, blood inparticular, to saturate this area of exposed hydrophilic matrix, is theneed to draw a greater volume of blood sample from the patient. Thisrequisite greater volume of sampled fluid requires use of a blood samplesize which is rather large for a typical finger stick, thusnecessitating use of a larger diameter needle and/or deeper penetrationinto the skin. These factors can increase the discomfort and pain feltby the patient, and may be difficult to achieve for those individualswhose capillary blood does not readily express. As this sampling processmay be repeated frequently within a single day, for many diabetics, anincrease in pain quickly becomes less tolerable or intolerable alltogether.

As such, there is a continuing need for a test device for use in analyteconcentration measurement that is easy to insert into and self-aligningwithin a meter, highly resistant to rebounding upon insertion and tomovement once operatively placed within the meter, and minimizes thevolume of the sample of biological fluid that is necessary to ensure anaccurate measurement.

Relevant Literature

Patents and publications of interest include: U.S. Pat. Nos. 4,935,346,5,049,487, 5,304,468 and 5,563,042.

SUMMARY OF THE INVENTION

The present invention is directed to fluid sampling and analytemeasurement devices, instrumentation, systems and kits, as well asmethods for using the same, which improve upon the prior art. Moreparticularly, test strips for holding a sampled fluid for measurement bya meter or an associated test strip holder are provided. The subjecttest strips may be provided in conjunction with a measurementinstrument, i.e., an analyte measurement meter, an analyte measurementsystem, a kit for analyte measurement and/or accessory devices.

The subject test devices are configured for insertion into a measurementinstrument or a test strip holder within a measurement instrument. Inmany embodiments, the subject test strips are in the form of a thin,flat strip defining a longitudinal axis, and include a distal edgesubstantially transverse to the longitudinal axis and an alignment notchformed in the distal edge for engagement with an alignment member or pinwithin the test strip holder of the meter or the meter itself. Thealignment notch has opposing edges wherein at least a portion of theseedges is substantially parallel to the longitudinal axis of the teststrip. The test devices further include an aperture for receiving avolume of a fluid sample that is less than that required by prior artdevices.

The subject test devices may include a support member and asample-absorbing member. The above-mentioned notch and aperture of thetest devices are features of the support member. Affixed to the bottomsurface of the support member is a sample-absorbing member in the formof a pad which covers the aperture. The pad is made of a hydrophilicmaterial and, as such, absorbs the fluid sample deposited on theaperture. A reagent material may be contained within the pad forfacilitating the measurement of the analyte targeted for measurement.

These and other features of the invention will become apparent to thosepersons skilled in the art upon reading the details of the presentinvention as more fully described below.

BRIEF DESCRIPTIONS OF THE DRAWINGS

FIG. 1A is a top view of a schematic representation of a prior art teststrip in operative engagement with the alignment pin of a meter's teststrip holder (not shown);

FIG. 1B is perspective view of the prior art test strip of FIG. 1A;

FIG. 2A is a top view of a schematic representation of the test strip ofthe present invention in operative engagement with the alignment pin ofa meter's test strip holder (not shown); and

FIG. 2B is enlarged view of the insertion end of the test strip of FIG.2A, illustrating the details of an optimized notch configuration and anoptimized sample application aperture.

DETAILED DESCRIPTION OF THE INVENTION

Before the present invention is described in further detail, it is to beunderstood that this invention is not limited to the particularembodiment described, as such may, of course, vary. It is also to beunderstood that the terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to belimiting, since the scope of the present invention will be limited onlyby the appended claims.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range is encompassed within the invention. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges is also encompassed within the invention, subject to anyspecifically excluded limit in the stated range. Where the stated rangeincludes one or both of the limits, ranges excluding either both ofthose included limits are also included in the invention.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any structure andmethod similar or equivalent to those described herein can also be usedin the practice or testing of the present invention, the preferredstructure and method of use are now described. All publicationsmentioned herein are incorporated herein by reference to disclose anddescribe the structures and/or methods in connection with which thepublications are cited.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “and”, and “the” include plural referents unless thecontext clearly dictates otherwise. Thus, for example, reference to “atest strip” includes a plurality of such test strips and reference to“the meter” includes reference to one or more meters and equivalentsthereof known to those skilled in the art, and so forth.

The publications discussed or cited herein are provided solely for theirdisclosure prior to the filing date of the present application. Nothingherein is to be construed as an admission that the present invention isnot entitled to antedate such publication by virtue of prior invention.Further, the dates of publication provided may be different from theactual publication dates which may need to be independently confirmed.

Overview

As summarized above, the subject invention provides an improved teststrip for use with a measurement apparatus, e.g., an analyte measuringmeter, to determine the existence and/or concentration level of analytepresent in a sample of fluid. The subject test strip is particularlysuitable for use with a photometric instrument or spectrometer for thedetermination of the glucose concentration in a sample of whole blood.

The advantages of the present invention will be better understood in thecontext of the following comparison with the exemplary prior art teststrip of FIGS. 1A and 1B, and the description of an exemplary embodimentof the test strip of the present invention as illustrated in FIGS. 2Aand 2B.

Prior Art Test Strip(s)

Referring now to FIG. 1A, there is shown a top view of a schematicrepresentation of one embodiment of a test strip 10 of the prior artoperatively engaged with an alignment pin 20, commonly provided on theinside distal edge of a test strip holder (now shown) or within theinside distal edge of a test strip receiving area within, the meteritself (not shown) for facilitating the alignment of test strip 10within a meter (not shown) for measurement of an analyte of interest.Such a test strip 10 is disclosed, for example, in U.S. Pat. No.5,563,042.

As is more clearly viewed in FIG. 1B, test strip 10 includes a supportmember 12, typically made of a plastic material or the like, by whichstrip 10 can be held. Support member 12 has length and width dimensionswhich are suitable for use with the test strip holder being used.Typically, the length dimension is in the range from about 15 to 60 mm,and the width dimension is in the range form about 5 to 20 mm. Mountedon either the top or bottom side of support member 12 is a reagentelement 11 in the form of a membrane, pad or the like, where matrix pad11 is typically made of a hydrophilic porous matrix and one or morereagents impregnated into the pores of the matrix. The one or morereagent(s) are selected based on the analyte targeted for measurementand, in the case of photometric measurement, is capable of reacting withthe target analyte to produce a compound that is characteristicallyabsorptive at a wavelength other than a wavelength at which the assaymedium substantially absorbs light. Reagent element 11 is directly andfirmly attached to support member 12 by means of a non-reactive adhesive13. Typically, the length dimension reagent element 11 is in the rangefrom about 5 to 20 mm, and the width dimension is in the range formabout 5 to 10 mm.

Aperture 14 is present in support member 12 in a portion of the area towhich reagent pad 11 is attached. Aperture 14 has a circularconfiguration having a diameter typically in the range from about 4.5 to5 mm. Accordingly, a typical surface area defined by circular aperture14 ranges from about 15.5 to 20 mm².

Support member 10 further comprises an alignment notch 15 in the form ofa “V” at distal edge 17 and about the y-axis or vertical centerline 18(see FIG. 1A) of support member 12. More particularly, notch 15 consistsof two straight segments 15 a, 15 b (one on each side of vertical centerline 18), each set at about a 45° angle with respect to verticalcenterline 18 wherein the proximal ends of segments 15 a, 15 b intersectat vertical centerline 18, forming the apex 15 c of notch 15. The distalends of legs 15 a, 15 b terminate, respectively, at points approximatelybetween about 2 to 4 mm from the strip's vertical centerline 18.

The measurement methodology using the above-described test strip 10involves the use of a measurement instrument or meter (not shown), suchas a diffuse reflectance spectrophotometer having suitable software,into which test strip 10 is operatively inserted. Generally, a suitablespectrophotometer includes a light source, such as one or more lightemitting diodes (LED), and a corresponding light reflectance detectorthat can be adapted to respectively generate and respond to light havinga particular wavelength. Such meters are commonly known by those skilledin the art of analyte measurement.

When operatively inserted into a test strip holder of a suitable meteror a meter itself without a holder, test strip 10 is moved in a forwardor distal direction until notch 15 is engaged with alignment pin 20. Theassay process begins by providing a sample containing the analyte to bemeasured and applying it to aperture 14 of test strip 10. Application ofthe sample to aperture 14 may occur either prior to or after insertionof test strip 10 into the test strip holder. Support member 12 holdsreagent pad 11 so that a sample can be applied to aperture 14 on the topsurface of support member 12 while light reflectance is measured fromthe bottom surface of support member 12, i.e., on the side of thereagent pad 11 opposite aperture 14. Generally, the normal volume ofsample applied is in the range from about 5 to 50 μl and more typicallyfrom about 12 to 30 μl. A beam of light is then generated and projectedonto the reagent pad 11 by a spectrophotometer, and the reflectance ofthe light created by the reaction between the reagent and the targetanalyte within the sample is then automatically measured at certaintimes. The meter's software then automatically calculates the rate ofchange of reflectance between measurements, and, using calibrationfactors, determines the level of analyte in the sample.

The purpose of the alignment notch and alignment pin arrangement is tofacilitate proper alignment of test strip 10 within the test stripholder such that aperture 14 is accurately aligned over the meter'slight source. Test strip 10 is allowed some movement about pin 20 atnotch 15 so that the side edges 16 of strip 10 will be properly seatedwithin the sides of the test strip holder (not shown). This is intendedto align aperture 14 over the light source within the measurement meter;however, it is this movement or lateral “play,” i.e., side-to-sideshifting, of test strip 10 that is often the cause of an improperlyaligned test strip.

Additionally, the V notch configuration has no means for specificallypreventing linear or longitudinal movement along the y-axis 18 of teststrip 10 once it is positioned within the test strip holder. Tocompensate for such movement, test strip 10 provides a large aperture 14requiring a greater volume of sample to be tested. Nonetheless, uponrebound, aperture 14 may be displaced enough such that none or aninsufficient amount of its interior surface area and the sampled fluidare aligned with the light source, resulting in an inaccuratemeasurement reading.

Test Strip(s) of the Present Invention

Referring now to FIG. 2A, there is shown a top view of a schematicrepresentation of a test device 30 of the present invention. In thisembodiment, test device 30 is in the form of a flat, thin rectangularconfiguration, i.e., a test strip, defining a longitudinal axis 38,however, it will be apparent to those of skill in the relevant art thatother shapes and/or configurations are also contemplated by thisinvention. Here, test strip device 30 is shown operatively engaged withan alignment pin 40 of a test strip holder (not shown). Test strip 30has the same or similar general functions and construct as test strip 10of FIGS. 1A and 1B, and is compatible with the types of measurementinstruments mentioned herein.

Test strip 30 includes a support member 32 which is adhesively engagedon its bottom surface with a sample absorbing element 31. Here, supportmember 32 is illustrated having a rectangular configuration andsample-absorbing element 31 is in the form of a rectangular padpositioned with its longitudinal axis transverse to the longitudinalaxis of that of support member 32. Although such rectangularconfigurations are illustrated, any configuration compatible with agiven measuring instrument is acceptable for test strip 30. In manyembodiments, support member 32 is made of a plastic material including,but not limited to, polystyrene, polyester, polyethylene. Support member32 may also be made from other suitable materials including, laminates,paper and composites, such as recycled plastics. In many embodiments,sample-absorbing pad 31 is made of a hydrophilic matrix, typicallyporous, or another suitable matrix for the analyte(s) targeted formeasurement. The matrix oftentimes contains at least one reagentmaterial selected for such targeted analyte(s). Support member 32 andreagent pad 31 of test strip 30 may have length, width and thicknessdimensions which are the same as or similar to that of support member 12and reagent pad 11 of test strip 10 of FIGS. 1A and 1B. In certainembodiments, support member 32 has a length in the range from about 15to 60 mm, a width in the range from about 5 to 20 mm, and a thickness inthe range from about 0.1 to 2.5 mm. In many embodiments, reagent pad 31has a length in the range from about 5 to 20 mm, a width in the rangefrom about 5 to 10 mm, and a thickness in the range from about 0.05 to 1mm.

The geometry and dimensions of both aperture 34 and notch 35 haveconfigurations which advantageously optimize the use of test strip 30.More particularly, aperture 34 of test strip 30 has a non-circular shapeand a smaller surface area than aperture 14 of prior art test strip 10.In many embodiments, aperture 34 has a shape or configuration that issubstantially “obround” which comprises two halves of a circle extendedapart by a straight midsection. Other possible configurations ofaperture 34 include, but are not limited to, oval, elliptical or oblong,having a major axial length dimension that is coaxial with the y-axis orvertical centerline 38 of test strip 30. The obround geometry ofaperture 34 is more specifically defined by top and bottom half circlesor arcs 34 a and 34 b and midsection 36. Arcs 34 a and 34 b are eachdefined by a base width in the range from about 3 to 6 mm, moretypically in the range from about 3.5 to 4 mm, and by an arc height inthe range from about 1.5 to 3 mm, more typically in the range from about1.75 to 2 mm. Midsection 36 has the same width as the base width of arcs34 a and 34 b, and a height (along y-axis 38) in the range from about0.1 to 0.2 mm, and more typically about 0.15 mm. The total y-axistangent-to-tangent dimension for aperture 34 equals twice the arcdiameter plus the length of midsection 36 and, thus, is in the rangefrom about 3.1 to 6.2 mm, and more typically from about 3.5 to 4.5 mm.Accordingly, the surface area defined by aperture 34 is in the rangefrom about 7 to 30 mm², and more typically in the range from about 10 to13.5 mm². Certain embodiments of the test strips of the presentinvention have an aperture surface area preferably no greater than about15 mm²

As such, the volume of the fluid sample necessary to provide an accuratemeasurement using test strip 30 of the present invention is less thanthat which is required when employing a prior art test strip. With theobround configuration of aperture 34, an amount of sample less thanabout 35 μl, and more typically less about 10 μl, and in certainembodiments, less than about 5 μl is required for an accuratemeasurement. Therefore, the volume of fluid sample, e.g., blood,necessary to be drawn from a patient is less than what is conventionallyrequired. Accordingly, relatively smaller needles, lancets and bloodletting devices or the like may be used for drawing the fluid samplefrom the patient or user of the device, thereby minimizing the pain anddiscomfort experienced by the patient during the sampling procedure, andminimizing the rate of non-compliance among patients.

As mentioned above, a test strip may have a tendency to spring back orrebound in a proximal direction upon contact with the distal end of thetest strip holder when being inserted into the test meter. Such proximaldisplacement of the test strip, and of the measurement aperture, is suchthat the aperture's exposure, and thus the sampled fluid's exposure, tothe light source beam of the meter is insufficient to provide anaccurate measurement reading of the sample deposited within theaperture. However, with the obround configuration of aperture 34, theshorter distance between apex 35 c to apex 40 of aperture 34, proximaldisplacement of test strip 30 within a nominal or typical distance willnot limit the area of aperture 34 exposed to the light source beam. Assuch, the extended apex-to-apex distance minimizes the effect ofrebounding by test strip 30. Additionally, this feature provides for anincreased insertion zone such that a sufficient surface area of aperture34 is exposed to the measurement source even when test strip 30 is notfully inserted into the test strip holder or meter. This in turnfacilitates a more accurate measurement of the sample and, over time,maximizes the repeatability of accurate measurements.

Alignment notch 35 also has a shape and configuration different fromthat of corresponding alignment notch 15 of prior art test strip 10.FIG. 2B illustrates an exemplary configuration of notch 35. Notch 35 hasopposing edges, one on each side of centerline 38. Preferably, theopposing edges are the same, i.e., mirror images of each other, orsubstantially similar. At least a portion of the opposing edges of notch35 is in substantially parallel relation with each other and withcenterline 38. Notch 35 may also include one or more segment pairs in anangular relation with centerline 38.

In the exemplary embodiment of FIGS. 2A and 2B, notch 35 is shown havingthree pairs of opposing edge segments 35 a and 35 b, 35 a′ and 35 b, and35 a″ and 35 b″. However, notch 35 may have more or fewer segment pairs,provided that the overall configuration of notch 35 provides stabilityto and substantially minimizes any shifting or movement of test strip 30when engaged within the meter.

Notch 35 consists of a first pair of edge segments 35 a, 35 b, one oneach side of centerline 38, each set at an angle α with respect tocenterline 38. Angle α preferably ranges from about 30° to 60°, and moretypically is about 45° from centerline 38. Segments 35 a, 35 b havelengths in the range from about 0.5 to 2.0 mm, and more typically in therange from about 0.7 to 1.25 mm. The respective distal ends of edgesegments 35 a, 35 b each extend laterally from centerline 38 a distancepreferably in the range from about 2.0 to 3.0 mm, and more typically inthe range from about 2.4 to 2.6 mm. The respective proximal ends of edgesegments 35 a, 35 b each extend inwardly from the respective distal endsand extend laterally from centerline 38 a distance preferably in therange from about 1.0 to 2.0 mm, and more typically in the range fromabout 1.5 to 1.7 mm.

The second pair of edge segments 35 a′ and 35 b′ extend downwardly fromthe proximal ends of segments 35 a, 35 b, respectively, and aresubstantially parallel to centerline 38. Segments 35 a′, 35 b′ havelengths preferably distance preferably in the range from about 0.5 to 2mm, and more typically in the range from about 0.9 to 1.1 mm.

The third pair of segments 35 a″ and 35 b″ extend inwardly from theproximal ends of segments 35 a′, 35 b′, respectively, each forming anangle β with centerline 38. Angle β preferably ranges from about 30° to60°, and more typically is about 45°. The proximal ends of segments of35 a″ and 35 b″ intersect at centerline 38. Fillets with radii in therange from about 0.2 to 0.4 mm may be added at each of the segmentjunctures to facilitate the manufacturing process.

The configuration of alignment notch 35 overcomes many of thedisadvantages of previous notch designs. In particular, the second pairof segments 35 a′, 35 b′ of notch 35, i.e., the segments that aresubstantially parallel to centerline 38, act to guide test strip 30 in astraight insertion path into a test strip holder or meter upon operativeengagement between notch 35 and alignment pin 40. Furthermore, suchconfiguration of notch 35 acts to minimize the likelihood of lateralmovement of the test strip upon insertion into the test strip holder ormeter. Additionally, edge segments 35 a′, 35 b′ maintain test strip 30in a straight and optimally aligned position within the test stripholder or meter after insertion and during the testing process byrestricting any lateral movement of test strip 30.

System(s) of the Present Invention

The present invention also includes systems for measuring theconcentration of at least one target analyte in a biological fluidsample. The subject systems include at least one of the subject teststrips and a measurement instrument. The measurement instrument may beany instrument adapted and suitable for measuring a targeted analyte ina fluid sample, including a physiological or biological fluid sample,such as interstitial fluid, blood, blood fractions, and the like. Thetest strips are particularly suitable for use with an optical orphotometric device (e.g., a spectrometer), but the test strips mayinclude components for use with an electrochemical measurementinstrument without departing from the scope of the invention.

The measurement meter typically includes a test strip holder into whichthe test strip is directly inserted, but the meter need not have such aholder. In either case, the meter has an alignment pin, either in thestrip holder or a test strip receptacle area of the meter. The alignmentnotch of the subject test strips has a configuration for engagement withthe alignment pin to ensure proper alignment of the test strip uponinsertion. Additionally, this notch-pin engagement maintains the teststrip in a substantially motionless position with respect to thealignment pin when said test strip is operatively engaged within thetest strip holder or meter, as described above.

Methods of Using the Test Strip(s) of the Present Invention

An exemplary method of the subject invention involves using at least onesubject test device in conjunction with a measurement instrument formeasuring the concentration of at least one constituent in a fluidsample. Also provided by the subject invention are methods of using thesubject devices, i.e., the test strips, to determine the existence andconcentration of chemical and biochemical components (analytes) inaqueous fluids. A variety of different constituents, e.g., analytes, maybe detected and their concentrations may be determined using the subjecttest strips, where representative constituents include glucose,cholesterol, lactate, alcohol, and the like. In many embodiments, thesubject methods are employed to determine the glucose concentration inan aqueous fluid, e.g., a biological fluid. While in principle thesubject methods may be used to determine the concentration of aconstituent in a variety of different biological samples, such as urine,tears, saliva, and the like, they are particularly suited for use indetecting and determining the concentration of a constituent in blood orblood fractions and more particularly whole blood.

In practicing the subject methods, the first step is to provide a testdevice, e.g., a test strip or the like, defining a longitudinal axis andhaving a distal edge which is substantially transverse to thelongitudinal axis, an aperture for receiving the fluid sample, asdescribed above, and an alignment notch formed in the distal edge forengagement with an alignment member of a measurement instrument, e.g., apin of a test strip holder or a pin in the receptacle area of a meter,wherein such an alignment notch has opposing edges where at least aportion of the opposing edges is in substantially parallel relation tothe longitudinal axis.

Either prior to or after insertion of the subject test strip into asuitable measuring instrument, a quantity of the biological sample isthen applied or introduced to the test strip, i.e., to the aperture ofthe test strip. The amount of biological sample, e.g., blood, that isapplied to the test strip may vary, but is generally less than about 5μl. The sample may be applied to the test strip using any convenientprotocol, where the sample may be injected, wicked, and the like. Inmany embodiments, e.g., colorimetric assays, the sample is allowed toreact with the reagent(s) of the test strip to produce a detectableproduct, as described above.

Automated meters for measuring the concentration of at least one of theconstituents in a biological sample deposited on the test strip for usewith colorimetric assays are well known in the art, for example see U.S.Pat. No. 5,059,395, the disclosure of which is herein incorporated byreference. The measurement instrument includes an alignment pinconfigured for engagement with the alignment notch of the test strip. Asmentioned above, the meter may include a test strip holder into whichthe test strip is directly inserted, but the meter need not have such aholder. In either case, the meter includes the alignment pin, either ina test strip holder or in the meter itself, e.g., in a test stripreceptacle area of the meter. Accordingly, upon insertion of the teststrip into the meter, the test strip, and more specifically thealignment notch of the test strip, is operatively engaged with thealignment pin of the measuring instrument. Specifically, the alignmentpin of the measurement instrument is operatively engaged between theopposing parallel edges of the test strip. In many embodiments, the teststrip is maintained in a substantially motionless position while it isoperatively engaged with the alignment pin. In other words, undesirable,unintended or unwanted movement or displacement of the test strip,lateral movement in particular, while the test strip is engaged with thealignment pin is substantially hindered, minimized or all togetherprevented due to the engagement of the notch and pin.

In certain embodiments, the subject methods further include minimizingthe effect of any proximal displacement of the test strip, if suchproximal displacement should occur. Accordingly, in many embodiments,the effect of proximal displacement is minimized by increasing theinsertion zone or area of the test strip, as described above. Forexample, in certain embodiments, the insertion zone is increased byextending or lengthening the depth of the alignment notch, as describedabove in reference to FIG. 2A (i.e., the distance between the alignmentnotch apex and the distal edges of the test strip is increased over theprior art) such that test device aperture is positioned closer to thedistal boundary of the meter or the test strip holder. As such, theaperture is more likely to remain within the measurement area, i.e., thearea in which the meter's light source is targeted, if such reboundingor proximal displacement (within a nominal or typical range) of testdevice does occur. In other embodiments, the insertion zone is increasedby decreasing the insertion gap, as described above. Regardless of theway in which the insertion zone is increased, the result of suchincrease minimizes the effect of any proximal displacement the teststrip may have.

Following insertion and operative engagement of the test strip withinthe measurement instrument, measurements are made. More specifically,the detectable product produced by the interaction of the biologicalsample and at least one reagent of the test strip is detected andrelated to the amount of constituent, e.g., analyte, in the sample bythe measurement instrument.

Additionally, the subject methods may further include repeating theabove-described method for a plurality of measurements of one or moresamples of fluid, wherein the measurement results are more accurate andhave better repeatability over the prior art.

Kits

Also provided by the subject invention are kits for use in practicingthe subject methods. The kits of the subject invention include at leastone subject test device or test strip. The kits may also include ameasurement instrumentation that may be used with reusable or disposabletest devices. Certain kits may include various test devices or teststrips having different sizes and/or containing the same or differentreagents. Additionally, the kits many include certain accessories suchas a means for sampling the fluid to be tested. For example, the meansfor sampling may include, but is not limited to, a needle, lancet orblood letting device for drawing from less than about 5 μl to about 10μl of blood from a patient. Finally, the kits preferably includeinstructions for using the subject devices and instrumentation in thedetermination of an analyte concentration in a fluid sample. Theinstructions for use may include, for example, language instructing theuser of the kit to apply less than about 35 μl, less than about 10 μl,or less than about 5 μl of the fluid sample to the test device. Theseinstructions may be present on one or more of the packaging, a labelinsert, or containers present in the kits, and the like.

It is evident from the above description that the features of thesubject test strip overcome many of the disadvantages of prior art teststrips including, but not limited to, minimizing the movement of thetest strip during and after insertion within a test strip holder,minimizing the detrimental effects of rebound and a lack of fullinsertion of the test strip if such should occur, and decreasing thevolume of fluid sample needed for an accurate measurement. Otheradvantages of the subject test strip are the reduction in painexperienced by a patient as a result of requiring a lower sample volumeand ensuring greater repeatability in the measurement process. As such,the subject invention represents a significant contribution to thefield.

The subject invention is shown and described herein in what isconsidered to be the most practical, and preferred embodiments. It isrecognized, however, that departures may be made there from, which arewithin the scope of the invention, and that obvious modifications willoccur to one skilled in the art upon reading this disclosure.

Although the present invention is useful for many applications, thesampling of various fluids and the detection of many types ofconstituents, the invention has been described primarily in the contextof the detection of analytes in biological fluid, and as beingparticularly useful for the detection of glucose in blood. Thus, thespecific devices and methods disclosed and the applications, biologicalfluids and constituents discussed herein are considered to beillustrative and not restrictive. Modifications that come within themeaning and range of equivalents of the disclosed concepts, such asthose that would readily occur to one skilled in the relevant art, areintended to be included within the scope of the appended claims.

1. A kit for measuring the concentration of at least one target analytein a sample of biological fluid, said kit comprising: (a) at least onetest strip having top and bottom surfaces, comprising: (i) asubstantially obround-shaped aperture for receiving a volume of fromabout 5 μL to about 10 μL of said sample of biological fluid; (ii) ahydrophilic pad affixed to one of said top or bottom surfaces andcovering said substantially obround-shaped aperture; and (iii) analignment notch comprising opposing parallel edges; and (b) ameasurement instrument comprising an alignment pin configured forengagement with said alignment notch wherein said test strip ismaintained in a substantially motionless position with respect to saidalignment pin when said test strip is operatively engaged within saidtest strip holder.
 2. The kit of claim 1 wherein said volume of saidsample is about 5 μL.
 3. The kit of claim 1 wherein said measurementinstrument is a spectrometer.